title: Confirmation of GRHL2 as the gene for the DFNA28 locus.
abstract: More than 10 years ago, a c.1609_1610insC mutation in the grainyhead-like 2 (GRHL2) gene was identified in a large family with nonsyndromic sensorineural hearing loss, so far presenting the only evidence for GRHL2 being an autosomal-dominant deafness gene (DFNA28). Here, we report on a second large family, in which post-lingual hearing loss with a highly variable age of onset and progression segregated with a heterozygous non-classical splice site mutation in GRHL2. The c.1258-1G>A mutation disrupts the acceptor recognition sequence of intron 9, creating a new AG splice site, which is shifted by only one nucleotide in the 3' direction. cDNA analysis confirmed a p.Gly420Glufs*111 frameshift mutation in exon 10.
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Vona
authors.forename: Indrajit
authors.initials: I
authors.lastname: Nanda
authors.forename: Cordula
authors.initials: C
authors.lastname: Neuner
authors.forename: Tobias
authors.initials: T
authors.lastname: Müller
authors.forename: Thomas
authors.initials: T
authors.lastname: Haaf
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D005799:Genes, Dominant; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C470830:GRHL2 protein, human; D014157:Transcription Factors; D004247:DNA
keywords: DFNA28; GRHL2; autosomal dominant hearing impairment; haploinsufficiency; postlingual hearing impairment; progressive hearing loss